Project Summary: Cardiovascular disease (CVD) remains the leading cause of death and disability for adults in the US. CVD and its risk factors disproportionately affect minorities and lower socioeconomic status (SES) Americans. Major strides have been made in treatment of CVD and control of some cardiometabolic risk factors (CRFs), but increasing prevalence of key CRFs, including obesity and diabetes, may limit future progress. Little is known about social determinants of CVD and mechanisms by which they may influence trajectories of CRFs and CVD. The interplay of genetic, environmental, behavioral and social determinants of CVD has not been well studied, due to lack of high-quality data in large diverse groups followed from birth to young adulthood. Since 2000, the Fragile Families and Child Wellbeing Study (FFCWS) has provided the social science community with data on a longitudinal birth cohort of nearly 5000 American children born in large cities and surveyed in multiple waves since birth. FFCWS contains a large number of racial and ethnic minorities: 47% Black children, 27% Hispanic children (17% children born to immigrant Hispanic parents). Approximately 40% of the families live below the poverty line. In addition to socioeconomic, demographic, neighborhood, and developmental data, our team has developed a large portfolio of genetic and epigenetic data for child participants. These features make the data unique among other large-scale, longitudinal studies, and thus well- suited for studying social determinants of the cardiovascular health (CVH) of vulnerable young adults. We propose to link this biologic and social science data with newly acquired measures of CVH including, among others: plasma biomarkers, anthropomorphic measurements, health-related behavior, and carotid ultrasound. We plan to transition the large FFCWS cohort of young adults, followed from birth through adolescence, into a longitudinal study of social determinants of health (SDoH) and their influence on CVH. We will perform an innovative in-person examination to measure all components of CVH and early evidence of subclinical cardiovascular disease (CVD). Our over-arching goal is to understand the role of early life adversity in the evolution of CVH and CVD, and potential epigenetic mediation. Our proposal is developed into three cohesive and interlocking aims: Aim 1: We will test associations of early life SDoH (see Table 1, Research Plan) collected in FFCWS with overall CVH status (14-point scale) and each of the 7 specific metrics of CVH, at approximately age 22 years (N=2400). Aim 2: We will assess associations of early life SDoH with the presence and extent of young adult subclinical CVD determined by carotid ultrasound in a subsample of FFCWS (n~1800). Aim 3: We will: a) examine temporal associations of epigenetic measures (DNA methylation, DNAm, at 9, 15, and 22 years) with upstream early life SDoH and downstream young adult CVH and subclinical CVD; b) explore potential mediation by DNAm of the discovered associations between early life SDoH and young adult CVH and subclinical CVD, accounting for known genetic effects on associations with CVH and subclinical CVD.